According to the American Cancer Society, about 1,529,560 new cancer cases are expected to be diagnosed in 2010 in the United States alone. Cancer is a condition where cell growth regulators do not function properly. As a result, cell growth exceeds cell death. Transforming Growth Factor-β-Activated Kinase 1(TAK1) inhibition is a mechanism to down-regulate cancer growth. Transforming growth factor-β1 (TGF-β1) cytokine regulates the composition of extracellular matrix (ECM), matrix proteolysis, and inflammatory responses. TGF-β1 suppresses tumor growth at early stages of cancer, whereas, at late stages, TGF-β1 promotes tumor spreading by through angiogenesis. Interference with TGF-β-activated protein kinase 1 (TAK1) activity alters TGF-β interactions with MMP-9 and the metastatic potential of cancer cells. See Safina et al., Oncogene 2008, 27, 1198-1207 (experiments showing that TAK1 RNA interference (siRNA) reduces expression of MMP-9 and tumor cell invasion). Thus, there is a need to identify improved TAK1 inhibitors useful in cancer treatments.
Hahn et al., Journal of Organometallic Chemistry, (2004), 689(16), 2662-2673, disclose the catalyzed reaction of 2-substituted furans with diazo compounds provides (2E,4Z)-2-arylhexadienedioic acid diesters. See also Hedley et al., J. Org. Chem., 2006, 71 (14), 5349-5356.